HEMAPROMPT by AERSCHER DIAGNOSTICS

HemaPrompt is a gualac-based in-vilro slide method for the qualitative detection of occult blood in feces and gastric aspirate or vomitus by medical professionals only.

For fecal testing, it is a useful ald In the diagnosis of a number of gastrointestinal disorders, and is recommended for use in 1) routine physical examinations 2) routine hospital testing 3) screening for colorectal cancer or gastro-Intestinal bleeding from any other source.

For the testing of gastric contents it is used for the early detection of occult blood in conditions such as gastric trauma, gastric or duodenal ulceration, gastric cancer, esophageal varices, situations of likely exogenous or endogenous gastrills, leukemia, and hereditary telangiectasia. These conditions may be encountered in the emergency room, recovery room or intensive care.

Device Description

The HemaPrompt slide, used with a buffered developer, is a guaiac based test for the detection of occult blood in both gastric and fecal samples. The test is not affected by low pH. When used with gastric specimens, it is free from interferences by normal therapeutic concentrations of iron, ranitidine, cimetidine and antacids.

When a gastric or fecal specimen containing blood is applied to the HemaPrompt test paper, hemoglobin from the lysed blood cells in the sample comes in contact with the guaiac in the paper. The developer, a buffered solution of alcohol and hydrogen peroxide, is applied by pulling the tab on the slide and creates a guaiac / peroxidase-like reaction in the presence of hemoglobin which in turn causes a blue coloration in the test paper. This test will turn blue in the presence of more than 2 mg Hb/ G stool and more than 200 mcg Hb/ ml gastric juice

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for HemaPrompt, based on the provided text:

Acceptance Criteria and Device Performance

Acceptance Criteria (Detection Limit)	Reported Device Performance (Fecal)	Reported Device Performance (Gastric)
Fecal: > 2 mg Hb/G stool	Reliably and definitely reacted at >= 2 mg Hb/G of stool within 60 seconds.	N/A
Gastric: > 200 mcg Hb/ml gastric juice	N/A	Reliably and definitely reacted at >= 200 mcg Hb/ml gastric juice within 60 seconds (for concentrations of 200 mcg/ml and greater, 100% positive reactions were observed).
Fecal: False Positive Rate for controlled diet < 1-2%	Not directly stated, but implicit due to use of "healthy volunteer on a diet" as baseline.	N/A
Gastric: No interference from normal therapeutic concentrations of iron, ranitidine, cimetidine, antacids.	N/A	No alteration of HemaPrompt results by normal therapeutic concentrations of ranitidine, ferrous sulfate, and an antacid (Mylanta).

Study Information

2. Sample Sizes Used for the Test Set and Data Provenance:

Fecal Study:
- Test Set: Not explicitly stated as a distinct "test set" sample size. The study used:
  - Stool from "a healthy volunteer on a diet" as a baseline.
  - Dilutions of blood (Hb 14G/dl by Coulter) in this stool to achieve concentrations of 0.1, 0.2, 0.4, and 0.6 grams hemoglobin per 100 grams of stool.
- Data Provenance: The text does not specify the country of origin. It appears to be a laboratory-based study using a single healthy volunteer, suggesting a prospective, controlled experimental setup rather than a broad clinical retrospective/prospective study.
Gastric Juice Study:
- Test Set:
  - 12 patient gastric samples (obtained by gastroscopy).
  - 8 healthy volunteer gastric samples (obtained by intubation).
- Data Provenance: The text does not specify the country of origin. Both patient and volunteer samples were collected prospectively for this study.
- Synthetic Gastric Juice (PBS):
  - Not explicitly a "test set" in the same clinical sense, but experimental samples were created by titrating PBS to various pH levels and adding hemoglobin concentrations of 50, 100, 200, and 500 mcg/ml. The number of samples for each condition isn't individually broken down, but percentages are given for 16 samples (e.g., 44% (7/16) at 50 mcg Hb/ml). This is a lab-based, prospective experiment.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

Fecal Study: The ground truth for the fecal study was established by precisely controlled dilutions of known hemoglobin concentrations into stool. There is no mention of human experts interpreting the "truth" of the fecal samples; it's based on the controlled addition of a known substance.
Gastric Juice Study: The ground truth for the gastric study was established by either:
- Known initial state: "None were positive initially" for patient samples, and "37.5% (3/8) were positive with no added blood" for volunteer samples.
- Controlled addition of known hemoglobin concentrations: Hemoglobin was added to samples to achieve specific concentrations (e.g., 50 mcg/ml, 100 mcg/ml, 200 mcg/ml, 500 mcg/ml).
- No human experts were used to establish the ground truth; it was based on controlled experimental conditions.

4. Adjudication Method for the Test Set:

Not applicable. The HemaPrompt test produces a visible blue coloration, indicating a positive result. The determination of a positive or negative reaction is objective based on the color change. There is no mention of an adjudication process by multiple readers for the HemaPrompt results themselves. For the ground truth, as noted above, it was based on known concentrations, not expert interpretation.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance:

No MRMC comparative effectiveness study was done. This device is a chemical test, not an AI-powered diagnostic tool. The document compares HemaPrompt's reactions to "another commercially available guaiac slide test" but this is a direct product-to-product comparison, not a human reader study.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

This is a standalone diagnostic test in the sense that its performance does not rely on a human interpreter beyond observing a color change. However, it is not an "algorithm" in the modern sense of AI. Its performance is chemical, directly responding to the presence of blood. The device itself is the "standalone" component producing the result.

7. The Type of Ground Truth Used:

Fecal Study: Experimentally controlled known concentrations of hemoglobin added to a baseline stool sample.
Gastric Juice Study:
- For clinical samples, it was the assumed initial state of the sample (e.g., "none were positive initially") and then known concentrations of added hemoglobin.
- For synthetic gastric juice, it was known concentrations of hemoglobin in a controlled pH environment.
- Essentially, the ground truth was based on known, controlled concentrations of the analyte (hemoglobin), rather than expert consensus, pathology, or outcomes data from a clinical population.

8. The Sample Size for the Training Set:

Not applicable. As a chemical diagnostic test that directly reacts to the target analyte, there is no "training set" in the context of machine learning or AI development. The device's reaction mechanism is inherent to its chemical composition, not learned from data.

9. How the Ground Truth for the Training Set Was Established:

Not applicable, as there is no training set for this type of device.

Summary

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HEMAPROMPT for use in detection of gastric and fecal occult blood. 510K SUMMARY OF

This summary of safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990.

As with any occult blood test, results with HemaPrompt cannot be conclusive evidence of the presence or absence of upper or lower bowel bleeding or pathology. HemaPrompt is designed for use as a preliminary screening aid and is not intended to replace other diagnostic procedures such as endoscopy or Xray procedures.

EXPECTED AND PERFORMANCE RESULTS

The use of guaiac impregnated paper for the detection of fecal occult blood has been extensively studied. These clinical studies indicate that guaiac impregnated slide tests yield a positive result 3-5% of the time in screening programs and the percent of false positive results lies in the range of 1-2% of persons on a controlled diet i.e. a diet excluding substances such as raw/ rare meat, and raw peroxidase-containing vegetables such as broccoli and cauliflower, with the normal daily fecal blood loss in an adult lying in the range of 1-2 mls. of blood per 100 gram of stool. Sensitivity (% of subjects with the condition being sought who test positive) is difficult to estimate, but in series of patients with known colorectal cancer, 50-87% have been reported to yield positive reactions. Estimates of positive reactions with adenomatous bleeding have varied widely, and appear dependant to a degree on the size of polyp, with polyps less than 2 cms yielding less than 5% positive reactions.

Feces Study: Stool from a healthy volunteer on a diet as described was used as a baseline specimen and assumed to contain 1 ml of blood / 100 G of stool which is about the normal daily blood loss of an adult. Blood (Hb 14G/dl by Coulter) was diluted in the stool by homogenization to provide concentrations of 0.1, 0.2, 0.4 and 0. 6 grams hemoglobin per 100 grams of stool. In an anemic person with a hemoglobin of 10G/dl these levels would be achieved with approximately 1, 2, 4 and 6 mls. of blood per 100 grams of stool. These dilutions were used to test the sensitivity of HemaPrompt as well as to compare the reactions to those obtained with another commercially available guaiac slide test concurrently with HemaPrompt on the same specimens four times on three occasions over a period of twelve days, with precautions taken to avoid specimen desiccation.

HemaPrompt reacted positively at total hemoglobin concentrations of 2mg/G of stool ( i.e. about twice the expected normal blood loss) or greater, in 60 seconds, with no reactions below this concentration. Hydrating stool (unless dried by adding distilled water may produce reactions below this level (2mg/G) by eluting blood out of the sample onto the test paper resulting in a possible false positive reaction.

It was concluded that with stool, HemaPrompt reacted reliably and definitely to all hemoglobin levels above 2mg/G of stool. It was also concluded that HemaPrompt with a buffered developer reacted in the same way as another commercially available guaiac test with buffering.

The significance of gastric occuit blood has been less extensively studied than fecal occult blood. One study of 153 gastric aspirates from 50 intubated healthy adults indicated all aspirates with more than 50 micrograms of hemoglobin/ ml were positive with a buffered guaiac impregnated test paper. There was an apparent overall false positive rate of 25.5% in this study of normal intubated individuals, but even using less than 25 micrograms of hemoglobin / ml. as the test cut-off. 11.8% showed a positive reaction. The positive rate will be affected by the method of collection. A traumatic

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intubation can be expected to produce some degree of bleeding .

Gastric Juice Study: HemaPrompt was studied with

a) 12 patient gastric samples obtained by gastroscopy.
...
b) 8 healthy volunteer gastric samples obtained by intubation.
c) samples of a synthetic gastric juice of Phosphate Buffered Saline (PBS) each titrated with HCI to give pH's ranging from 1.0 to 7.0 and hemoglobin concentrations of 50, 100, 200 and 500 mog/ml.

(a) It was found of the patient samples, none were positive initially, 37.5% (3/8) were positive with blood added to produce a concentration of 50 mcg / ml Hb, and 66% (8/12) were positive with 100 mcg / ml Hb and 100% of samples with blood added in concentrations of 200 mcg Hb / ml or greater reacted positively.

(b) Of the volunteer samples, 37.5% (3/8) were positive with no added blood. 60% (3/5) were positive with 20 mcg/ml Hb added, 87.5% (7/8) were positive with 50 mcg/ml Hb added to the specimen. and 100% were positive at concentrations of 100 mcg / ml and greater of added hemoglobin. All samples with blood added in concentrations of 200 mcg Hb / ml or greater reacted positively, and all reacted in less than 60 seconds. The positive rate will be affected by the method of collection. A traumatic intubation can be expected to produce some degree of bleeding. An initial negative result under these circumstances assumes added weight compared to a positive result ..

(c) Of the PBS samples, 50 mcg Hb/ mi produced a positive reaction 44% (7/16) of the time, with 100 mcg / ml 81.25% (13/16) of samples showed a positive reaction. At 200 mcg / ml and above all samples showed a positive reaction. Furthermore, concentrations of ranitidine, ferrous, suffate, and an antacid (Mylanta) to be expected in the stomach after a maximum recommended dosing did not alter the HemaPrompt results. This does not necessarily apply in overdose situations when excessive iron compounds and certain H2 blockers (e.g. cimetidine/Tagamet) could produce false positive reactions, and excess antacid or Zantac (ranitidine) could produce a false negative.

The samples from each person were repeated over a two week period. Results demonstrated excellent HemaPrompt reproducibility at levels above 200 mog/ ml gastric juice with all samples stored up to 10 days at 5℃ and showed excellent comparison to results obtained on the same samples with another commercially available test for this purpose

It was concluded that with gastric juice. HemaPrompt reacted reliably and definitely to hemoglobin levels above 200mcg / ml. gastric juice.

All monitors reacted in the expected manner (+ve turned blue ). Exposing the gualac paper to UV light for ten minutes inactivated the expected reaction.

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OCT 2 0 1997

Image /page/2/Picture/2 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features the department's name in a circular arrangement around an emblem. The emblem consists of a stylized caduceus, a symbol often associated with medicine and healthcare. The caduceus is depicted with three intertwined lines, representing the three branches of government, and a stylized eagle's head.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Robert Schreiber, M.D. CEO Aerscher Diagnostics, Inc. 359 High Street Chestertown, Maryland 21620

Re : K972763 Trade Name: HemaPrompt for Fecal and Gastric Occult Blood Regulatory Class: II Product Code: KHE Dated: July 22, 1997 Received: July 24, 1997

Dear Dr. Schreiber:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions aqainst misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Requlation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Druq Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Reqister. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) Additionally, for questions on the promotion and 594-4588. advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the requlation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page 1 of 1 -

510(k) Number (if known):_ K972763

Device Name:__________________________________________________________________________________________________________________________________________________________________

Indications For Use:

HemaPrompt is a gualac-based in-vilro slide method for the qualitative detection of occult blood in feces and gastric aspirate or vomitus by medical professionals only.

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(Division Sign-Off) Division of Clinical Laboratory Devices 510(k) Number

Prescription Use √
(Per 21 CFR 801.109)

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Over-The-Counter Use --

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Regulation Number and Section

§ 864.6550 Occult blood test.

(a)
Identification. An occult blood test is a device used to detect occult blood in urine or feces. (Occult blood is blood present in such small quantities that it can be detected only by chemical tests of suspected material, or by microscopic or spectroscopic examination.)(b)
Classification. Class II (special controls). A control intended for use with an occult blood test is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.